Until 2008, two types were recognized, complicated skin and skin structure infection (cSSSI) and uncomplicated skin and skin structure infection (uSSSI).[1] "Uncomplicated" SSSIs included simple abscesses, impetiginous lesions, furuncles, and cellulitis. "Complicated" SSSIs included infections either involving deeper soft tissue or requiring significant surgical intervention, such as infected ulcers, burns, and major abscesses or a significant underlying disease state that complicates the response to treatment. Superficial infections or abscesses in an anatomical site, such as the rectal area, where the risk of anaerobic or gram-negative pathogen involvement is higher, should be considered complicated infections.[2] The two categories had different regulatory approval requirements. The uncomplicated category (uSSSI) is normally only caused by Staphylococcus aureus and Streptococcus pyogenes, whereas the complicated category (cSSSI) might also be caused by a number of other pathogens. In cSSSI, the pathogen is known in only about 40% of cases.

Because cSSSIs are usually serious infections, physicians do not have the time for a culture to identify the pathogen, so most cases are treated empirically, by choosing an antibiotic agent based on symptoms and seeing if it works. For less severe infections, microbiologic evaluation via tissue culture has been demonstrated to have high utility in guiding management decisions.[3] To achieve efficacy, physicians use broad-spectrum antibiotics. This practice contributes in part to the growing incidence of antibiotic resistance, a trend exacerbated by the widespread use of antibiotics in medicine in general. The increased prevalence of antibiotic resistance is most evident in methicillin-resistant Staphylococcus aureus (MRSA). This species is commonly involved in cSSSIs, worsening their prognosis, and limiting the treatments available to physicians. Drug development in infectious disease seeks to produce new agents that can treat MRSA.[citation needed]